Description of Core Service Plan: The primary purpose ofthe Molecular Profiling and Pathology (MPP) Core is to provide the investigators in this POl with a centralized and coordinated resource for the analysis of human lung cancer samples and animal model tissues using morphologic and high throughput molecular methods (histopathology, immunohistochemistry, in situ hybridization, genomic and proteomic analyses). The MPP Core functions within this POl are grouped into four logically connected Aims or activities. 1. Procurement of human lung cancer tissues for validation studies. The Core will serve as the centralized resource for validation studies using human lung cancer samples procured under several MKSCC IRBapproved protocols. For rebiopsy protocols (non-therapeutic rebiopsy after treatment initiation or rebiopsy upon progression due to presumed acquired resistance), the Gore will also serve as the main tissue repository. 2. Pathology review & analysis. The MPP core will provide expert histologic and cytologic evaluation and classification of all human lung cancer specimens used in the POl, including morphologybased assays (IHC, GISH, FISH). The MPP will also provide expert histopathologic review of lung tumors in mouse models as well as xenografted human tumors. 3. Genotyping of human lung cancer tissues for validation studies. The MPP Gore has established and is further developing prospective genotyping efforts to provide extended mutational annotation of its human lung tumor resources that is critical for rational, welldesigned validation studies biologically relevant to specific leads arising from the Research Projects. 4. Coordination of validation studies using fully annotated human lung cancer tissues. The activities described in Aims 1-3 will provide a rich collection of rigorously classified human lung cancer tissues annotated for key lung cancer genes. Studies needed to validate the discoveries generated by the individual research projects in human lung cancer tissues will be performed in or coordinated by Core personnel. Robust platforms are established for DNA, RNA and protein analytes, with the specific validation analyses being determined by the questions to be answered by the individual Research Projects.